Variation in human genetic polymorphisms, their association with Helicobacter pylori acquisition and gastric cancer in a multi-ethnic country

Background and Aim: The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer‐related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients. Methods: Thirty‐four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models. Result: The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per‐allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2‐1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B‐1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2‐330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13‐1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection. Conclusion: These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection.